OTAR3088/BioData-CL_Article-Sentences · Datasets at Hugging Face

PMCID string	Title string	Sentences string
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Approximately 10–15% of GISTs do not harbor KIT or PDGFRA mutations and are generally insensitive to tyrosine kinase inhibitors.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The most common tumorigenic aberrations in these GISTs include deleterious mutations in succinate dehydrogenase (SDH) enzyme complex subunit genes SDHA, SDHB, SDHC, and SDHD and gene silencing epimutations of SDHC .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Additionally, rare pathway-activating driver mutations in the RAS/RAF/MAPK pathway, affecting genes such as BRAF and NF1, and ETV6-NTRK3 fusions have been reported .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Importantly, in these rare cases, BRAF mutations and NTRK fusions may enable targeted therapy with specific inhibitors, such as NTRK inhibitors larotrectinib and entrectinib, and BRAF or combined BRAF and MEK targeting therapies .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Phosphodiesterase 3 A (PDE3A) is an emerging therapeutic target in GIST.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Previous studies indicate that 90–100% of GISTs express PDE3A, and its expression is high compared with other tumor types or healthy tissues [10–12].
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	PDE3A is also expressed in interstitial cells of Cajal (ICC), which are the presumed precursors of GIST and play a role in regulating ICC development and network density in the gastrointestinal tract .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Interestingly, PDE3A silencing or inhibition of its enzyme activity does not impair the viability of GIST cells .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Instead, PDE3A has a structural role as a protein complex partner with Schlafen 12 (SLFN12), which is co-expressed in 92% of GISTs .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	PDE3A modulators, such as anagrelide, nauclefin, and DNMDP, act as molecular glues, inducing protein–protein interaction between PDE3A and SLFN12.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The formation of the PDE3A-SLFN12 complex leads to increased cytoplasmic SLFN12 stability and ultimately cell death-inducing RNase activity in the cells [14–16].
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Notably, two of these modulators, anagrelide and OPB-171775, have demonstrated significant anti-tumor efficacy in patient-derived GIST xenograft mouse models, including those resistant to tyrosine kinase inhibitors .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Additionally, both compounds have shown synergy with imatinib in GIST PDX mouse models .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Although several studies have reported high PDE3A expression in GISTs, its potential role as a prognostic or diagnostic biomarker remains uncharacterized.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	In this study, we examined PDE3A expression in 173 formalin-fixed paraffin-embedded (FFPE) GIST tumor samples using a novel mouse monoclonal antibody and immunohistochemistry (IHC).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	We also investigated the correlation between PDE3A mRNA and protein expression.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Additionally, we analyzed the association between PDE3A expression, GIST genotype, clinicopathological factors, SLFN12 expression and survival.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Two retrospective series of FFPE GIST tissue samples were analyzed.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The first series, collected from the Helsinki Biobank (Helsinki, Finland), included 161 samples.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Tumors were diagnosed at Helsinki University Hospital (HUH) between 1990 and 2020, and corresponding clinical data (Table 1) were retrieved from the HUH data lake, as described earlier .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Metastasis-free survival data were updated from radiology reports, with 53 cases missing this information (data collection closed on 18 April 2023).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Fourteen cases were excluded due to missing clinical information, misdiagnosis after histological re-evaluation, insufficient tissue, or samples not from primary tumors, leaving 147 cases for analysis.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Tissue microarrays (TMAs) were constructed from three to six 1.0 mm core punches per tumor sample.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were analyzed by Sanger sequencing, and CD117 expression was assessed via immunohistochemistry on TMA, as described elsewhere .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	GISTs were stratified into risk categories based on the Modified National Institutes of Health (M-NIH) system, omitting tumor rupture due to missing data .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Nine patients had metastases at diagnosis.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Table 1PDE3A expression and tumor characteristics in 147 GISTsCharacteristicPDE3A expressionP-valueLow (n = 7)Intermediate (n = 50)High (n = 90)Sex, n (%)0.584 Male (n = 73)3 (42.9)28 (56.0)42 (46.7) Female (n = 74)4 (57.1)22 (44.0)48 (53.3) Median age at diagnosis (range), years57 (50–75)67 (36–91)65 (10–89)0.434* Median tumor diameter (range), cm5.5 (2.5–8.5)6.0 (0.9–22.0)5.1 (1.0–29.0)0.579* NA22 Median mitotic count per 50 HPF (range)1 (0–5)4 (0–39)5 (0–100)0.007* NA12Location, n (%) Gastric (n = 105)5 (71.4)35 (70.0)66 (73.3)0.938 Intestinal (n = 35)2 (28.6)13 (26.0)20 (22.2) Extragastrointestinal (n = 7)0 (0)2 (4.0)4 (4.4)Risk category, n (%) Very low (n = 4)0 (0)3 (6.8)1 (1.2)0.500 Low (n = 45)1 (25.0)14 (31.8)29 (34.9) Intermediate (n = 28)2 (50.0)9 (20.5)17 (20.5) High (n = 62)1 (25.0)18 (40.9)36 (43.4) NA124Metastasis at diagnosis, n (%) Absent (n = 138)5 (71.4)46 (92.0)87 (96.7)0.040 Present (n = 9)2 (28.6)4 (8.0)3 (3.3) Mutated gene and exon, n (%)> 0.222 KIT/PDGFRA wild type (n = 22)1 (14.3)6 (12.0)15 (16.7) KIT exon 9 (n = 11)1 (14.3)5 (10.0)5 (5.6) KIT exon 11 (n = 85)4 (57.1)23 (46.0)59 (65.6) KIT exon 13 (n = 6)0 (0)2 (4.0)3 (3.3) PDGFRA exon 12 (n = 2)0 (0)2 (4.0)0 (0) PDGFRA exon 18 (n = 17)1 (14.3)9 (18.0)7 (7.8) NA31CD117 staining intensity, n (%) < 0.001 Negative1 (14.3)0 (0)0 (0) Weak1 (14.3)9 (18.0)3 (3.3) Intermediate2 (28.6)12 (24.0)5 (5.6) Strong3 (42.9)29 (58.0)82 (91.1)Schlafen 12 staining, n (%)0.083 Negative4 (57.1)12 (24.0)35 (38.9) Positive3 (42.9)38 (76.0)55 (61.1)NA Not availableAssociation investigated between continuous variables and PDE3A expression using the Kruskal–Wallis test PDE3A expression and tumor characteristics in 147 GISTs NA Not available Association investigated between continuous variables and PDE3A expression using the Kruskal–Wallis test The second GIST series consists of 26 FFPE tumor samples on TMAs, collected at the National Paediatric and Adult Wild-Type GIST and GIST Clinic at Cambridge University Hospitals NHS Foundation Trust, UK.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Their mutations were analyzed using Sanger sequencing, as described elsewhere .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The tumors harbored mutations in the following genes: KIT (n = 6), PDGFRA (n = 4), NF1 (n = 4), or one of the SDH genes (SDHA, SDHB, SDHC, SDHD, n = 12).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The study on the GIST and liposarcoma series collected from Helsinki Biobank was approved by the Ethics Committee IV of HUH (HUS/1258/2020).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Permission to use tissue samples and clinical data was granted by Helsinki Biobank (HUS/430/2021 §4) and HUH (HUS/244/2021).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Project-specific consent for this retrospective study was waived since the Finnish Biobank Act provides a lawful basis for research use.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The study of GIST samples collected from Cambridge was approved by Cambridge South Research Ethics Committee (REC reference number CA/5175) and all patients provided informed consent.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Mouse monoclonal anti-PDE3A antibodies were produced by immunizing mice with a peptide (amino acids 669–1141) from the catalytic domain of PDE3A (ProteoGenix SAS, Schiltigheim, France) and provided for the study by Sartar Therapeutics Ltd. (Helsinki, Finland).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	After spleen cell fusion and screening of hybridoma supernatants by ELISA, 99 positive clones were identified.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	From these, the supernatants of the 20 clones with the highest binding affinity were selected for testing in immunohistochemistry on FFPE colon tissue, using interstitial cells of Cajal as a positive control for specific staining.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The four clones that showed the highest specificity were subcloned and monoclonal antibodies affinity-purified and further investigated using immunohistochemistry.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Finally, clone 230-F8-G1 was selected to be used in immunohistochemistry.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	TMA Sects. (
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	3 µm thick) were placed on Superfrost® Plus objective slides (Thermo Scientific, MA, USA) and warmed at 56 °C for 30 min following paraffin removal in xylene, followed by a graded alcohol-to-water wash.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Endogenous peroxidase activity was blocked by incubating the slides in 0.8% hydrogen peroxide for 30 min.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Heat-induced epitope retrieval was performed using EnVision FLEX Target Retrieval LOW Solution (Cat# K8005, pH 6.0; Dako, CA, USA) in a HIER Decloaking Chamber (Biocare Medical, CA, USA) at 95 °C for 15 min.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The PDE3A antibody was diluted to 9.2 µg/mL in ImmunoLogic Normal Antibody Diluent (Cat# BD09-500, WellMed, Duiven, Netherlands) and incubated on tissues for 30 min at room temperature in a humidity chamber.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	A secondary antibody (BrightVision 1-step detection system rabbit HRP, Cat# DPVM110HRP, WellMed) was then applied for 30 min under the same conditions.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Antibody binding was detected using the ImmPACT DAB Substrate kit (Cat# SK4105, Vector Laboratories, CA, USA) for 5 min.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	SLFN12 expression was assessed as previously described, using a polyclonal SLN12 rabbit antibody (Cat# PA5-114360, Thermo Scientific) .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Finally, tissues were counterstained with Mayer’s Hematoxylin (Cat# S3309, Dako) for 3 min at room temperature, then dehydrated through a graded alcohol series to xylene.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Sections were washed with Tris-buffered saline containing 0.1% Tween-20 before and after antibody incubation steps.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	CD117 expression was assessed as described elsewhere .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Syncytiotrophoblasts in placental tissue served as a positive control for SLFN12 staining, and staining intensity was categorized as either negative or positive.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Interstitial cells of Cajal in colon tissue served as a positive control for PDE3A staining.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Bone marrow tissue for megakaryocyte PDE3A expression was also assessed.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The stained slides were digitalized using a 20 × objective and with a Panoramic scanner (3DHISTECH, Budapest, Hungary) in Helsinki Biobank and scored manually using SlideViewer software (version 2.7.0.191696, 3DHISTECH).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Due to the homogeneous staining pattern, PDE3A staining intensity was graded into four categories: absent, low, intermediate, and strong (0 to 3).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	GISTs were analyzed independently by three pathologists (O.G., M.S., T.B.).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	For statistical analysis, the average of the scores was calculated and rounded to the nearest whole number.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	RNA was extracted from 30 GIST and 10 liposarcoma FFPE tissue sections using QIASymphony RNA kit and QIASymphony SP instrument (Qiagen GmbH, Hilden, Germany), and 2 µL of RNA (30 to 300 ng) was reverse-transcribed into cDNA using SuperScript™ VILO™ cDNA synthesis kit (Cat# 11754250, Thermo Ficher Scientific, Carlsbad, CA, USA) following the manufacturer’s instructions, as described earlier .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	RNA extracted from the FFPE sample made from the GIST882 cell line was used as a reference sample.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Quantitative PCR was conducted using QuantiNova Probe PCR kit (Cat# 208254, Qiagen), and primers and probe in a ready-to-use mixture for PDE3A expression were designed with QuantiNova LNA PCR software (https://geneglobe.qiagen.com/fi/customize/pcr/mrna-incrna/quantinova-lna-probe-pcr-custom-assays).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	YWHAZ served as a reference gene (Forward: 5´-CGT TAC TTG GCT GAG GTT GC-3’; Reverse: 5’ -TGC TTG TTG TGA CTG ATC GAC-3’; Probe #9: Cat# 04683633001, Universal ProbeLibrary, Roche, Basel, Switzerland).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Real-time PCR was performed using the CFX96 Real-Time System (Bio-Rad Laboratories Inc., Hercules, CA, USA) to triplicate samples under following cycling: initial denaturation at 95 °C for 2 min, followed by 50 cycles at 95 °C for 30 s and at 60 °C for 30 s with plate reading.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Relative PDE3A mRNA expression was calculated using the ΔΔCt method and normalized to YWHAZ expression.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Crosstabs were analyzed using either Fisher’s exact test or Fisher–Freeman–Halton test.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The association between PDE3A expression and continuous variables was analyzed using the Kruskal–Wallis test.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Inter-rater concordance was estimated using Fleiss’ kappa analysis.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Overall survival was calculated from the date of diagnosis to the date of death, and metastasis-free survival from the date of diagnosis to the date of detected metastasis, censoring the patients without events at the end of follow-up.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Survival was estimated using the Kaplan–Meier method and compared using a log-rank test.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Statistical analyses were performed using IBM SPSS Statistics version 29.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Immunohistochemical staining of PDE3A was first investigated in healthy colon tissue.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	We observed strong PDE3A staining in interstitial cells of Cajal, the suggested precursors of GIST, and in mast cells (Fig. 1).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Additionally, endocrine cells within villi, endothelial cells, and ganglia showed weaker expression.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Contrary to a previous study , we did not observe staining in thrombocytes or megakaryocytes in two bone marrow samples, although histiocytes showed granular staining pattern.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Fig. 1Examples of immunohistochemical stainings in healthy and tumor tissues.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	PDE3A expression in (A) Interstitial cells of Cajal, B neuroendocrine epithelial cells and mast cells, and (C) ganglia cells in colon.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Examples of (D) weak, E intermediate, and F) strong staining of PDE3A in GISTs.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	G PDE3A staining was absent in megakaryocytes and showed granular staining in histiocytes in bone marrow tissue samples.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	H Examples of SLFN12-negative and (I) SLFN12-positive and (J) weak, K intermediate, and (L) strong CD117 staining in GISTs.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Each field of view corresponds to 0.2 mm × 0.2 mm Examples of immunohistochemical stainings in healthy and tumor tissues.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	PDE3A expression in (A) Interstitial cells of Cajal, B neuroendocrine epithelial cells and mast cells, and (C) ganglia cells in colon.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Examples of (D) weak, E intermediate, and F) strong staining of PDE3A in GISTs.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	G PDE3A staining was absent in megakaryocytes and showed granular staining in histiocytes in bone marrow tissue samples.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	H Examples of SLFN12-negative and (I) SLFN12-positive and (J) weak, K intermediate, and (L) strong CD117 staining in GISTs.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Each field of view corresponds to 0.2 mm × 0.2 mm An IHC analysis was conducted on the GIST series from Cambridge, where all 26 GISTs were positive for PDE3A staining.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Of these, four (15.4%) had weak, 12 (46.2%) intermediate, and 10 (38.5%) strong staining (Supplementary Table 1).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Similarly, in the Helsinki Biobank series, all GISTs (n = 147) expressed PDE3A with staining intensity varying; seven cases (4.8%) showed weak, 50 (34%) intermediate, and 90 (61.2%) strong staining.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Weak to strong PDE3A expression was observed in all investigated GISTs (Fig. 1; Supplementary Fig. 1).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Inter-rater agreement among the three pathologists for the results from the Helsinki Biobank series was assessed using Fleiss'kappa.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The analysis yielded a kappa (κ) value of 0.692 (standard error = 0.048, 95% confidence interval = 0.60 to 0.79, p < 0.001), indicating substantial agreement between the raters.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Next, we investigated the correlation between PDE3A protein and mRNA expression in GIST and pleomorphic liposarcoma tissues.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Pleomorphic liposarcomas were selected for the comparison as they contain frequently low PDE3A mRNA and protein expression .
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	RT-qPCR was successfully performed on 23 GIST and 10 liposarcoma samples.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Tissue for IHC was available in all GISTs and in 7 liposarcomas.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Relative mRNA expression levels were compared with RNA extracted from a FFPE GIST882 cell line.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	The results demonstrated that PDE3A mRNA expression is significantly higher in GISTs than in liposarcomas (median relative gene expression: 2.30 vs. 0.03, p < 0.001; Fig. 2; Supplementary Table 2).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	In addition, PDE3A protein and mRNA expression levels showed a strong positive correlation (p < 0.001).Fig.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	2Comparison of relative PDE3A mRNA expression and PDE3A protein expression in 23 GIST and 10 liposarcoma tissues.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Immunohistochemistry results were missing for three liposarcomas.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Three GISTs with intermediate staining were grouped in the strong staining category.
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	A PDE3A mRNA expression was significantly higher in GISTs than in liposarcomas (p < 0.001).
PMC12647229	Phosphodiesterase 3 A expression in gastrointestinal stromal tumors	Examples of (B) PDE3A-negative and (C) PDE3A weak staining in liposarcomas.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Approximately 10–15% of GISTs do not harbor KIT or PDGFRA mutations and are generally insensitive to tyrosine kinase inhibitors.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The most common tumorigenic aberrations in these GISTs include deleterious mutations in succinate dehydrogenase (SDH) enzyme complex subunit genes SDHA, SDHB, SDHC, and SDHD and gene silencing epimutations of SDHC .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Additionally, rare pathway-activating driver mutations in the RAS/RAF/MAPK pathway, affecting genes such as BRAF and NF1, and ETV6-NTRK3 fusions have been reported .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Importantly, in these rare cases, BRAF mutations and NTRK fusions may enable targeted therapy with specific inhibitors, such as NTRK inhibitors larotrectinib and entrectinib, and BRAF or combined BRAF and MEK targeting therapies .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Phosphodiesterase 3 A (PDE3A) is an emerging therapeutic target in GIST.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Previous studies indicate that 90–100% of GISTs express PDE3A, and its expression is high compared with other tumor types or healthy tissues [10–12].

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

PDE3A is also expressed in interstitial cells of Cajal (ICC), which are the presumed precursors of GIST and play a role in regulating ICC development and network density in the gastrointestinal tract .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Interestingly, PDE3A silencing or inhibition of its enzyme activity does not impair the viability of GIST cells .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Instead, PDE3A has a structural role as a protein complex partner with Schlafen 12 (SLFN12), which is co-expressed in 92% of GISTs .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

PDE3A modulators, such as anagrelide, nauclefin, and DNMDP, act as molecular glues, inducing protein–protein interaction between PDE3A and SLFN12.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The formation of the PDE3A-SLFN12 complex leads to increased cytoplasmic SLFN12 stability and ultimately cell death-inducing RNase activity in the cells [14–16].

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Notably, two of these modulators, anagrelide and OPB-171775, have demonstrated significant anti-tumor efficacy in patient-derived GIST xenograft mouse models, including those resistant to tyrosine kinase inhibitors .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Additionally, both compounds have shown synergy with imatinib in GIST PDX mouse models .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Although several studies have reported high PDE3A expression in GISTs, its potential role as a prognostic or diagnostic biomarker remains uncharacterized.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

In this study, we examined PDE3A expression in 173 formalin-fixed paraffin-embedded (FFPE) GIST tumor samples using a novel mouse monoclonal antibody and immunohistochemistry (IHC).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

We also investigated the correlation between PDE3A mRNA and protein expression.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Additionally, we analyzed the association between PDE3A expression, GIST genotype, clinicopathological factors, SLFN12 expression and survival.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Two retrospective series of FFPE GIST tissue samples were analyzed.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The first series, collected from the Helsinki Biobank (Helsinki, Finland), included 161 samples.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Tumors were diagnosed at Helsinki University Hospital (HUH) between 1990 and 2020, and corresponding clinical data (Table 1) were retrieved from the HUH data lake, as described earlier .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Metastasis-free survival data were updated from radiology reports, with 53 cases missing this information (data collection closed on 18 April 2023).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Fourteen cases were excluded due to missing clinical information, misdiagnosis after histological re-evaluation, insufficient tissue, or samples not from primary tumors, leaving 147 cases for analysis.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Tissue microarrays (TMAs) were constructed from three to six 1.0 mm core punches per tumor sample.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were analyzed by Sanger sequencing, and CD117 expression was assessed via immunohistochemistry on TMA, as described elsewhere .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

GISTs were stratified into risk categories based on the Modified National Institutes of Health (M-NIH) system, omitting tumor rupture due to missing data .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Nine patients had metastases at diagnosis.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Table 1PDE3A expression and tumor characteristics in 147 GISTsCharacteristicPDE3A expressionP-valueLow (n = 7)Intermediate (n = 50)High (n = 90)Sex, n (%)0.584 Male (n = 73)3 (42.9)28 (56.0)42 (46.7) Female (n = 74)4 (57.1)22 (44.0)48 (53.3) Median age at diagnosis (range), years57 (50–75)67 (36–91)65 (10–89)0.434* Median tumor diameter (range), cm5.5 (2.5–8.5)6.0 (0.9–22.0)5.1 (1.0–29.0)0.579* NA22 Median mitotic count per 50 HPF (range)1 (0–5)4 (0–39)5 (0–100)0.007* NA12Location, n (%) Gastric (n = 105)5 (71.4)35 (70.0)66 (73.3)0.938 Intestinal (n = 35)2 (28.6)13 (26.0)20 (22.2) Extragastrointestinal (n = 7)0 (0)2 (4.0)4 (4.4)Risk category, n (%) Very low (n = 4)0 (0)3 (6.8)1 (1.2)0.500 Low (n = 45)1 (25.0)14 (31.8)29 (34.9) Intermediate (n = 28)2 (50.0)9 (20.5)17 (20.5) High (n = 62)1 (25.0)18 (40.9)36 (43.4) NA124Metastasis at diagnosis, n (%) Absent (n = 138)5 (71.4)46 (92.0)87 (96.7)0.040 Present (n = 9)2 (28.6)4 (8.0)3 (3.3) Mutated gene and exon, n (%)> 0.222 KIT/PDGFRA wild type (n = 22)1 (14.3)6 (12.0)15 (16.7) KIT exon 9 (n = 11)1 (14.3)5 (10.0)5 (5.6) KIT exon 11 (n = 85)4 (57.1)23 (46.0)59 (65.6) KIT exon 13 (n = 6)0 (0)2 (4.0)3 (3.3) PDGFRA exon 12 (n = 2)0 (0)2 (4.0)0 (0) PDGFRA exon 18 (n = 17)1 (14.3)9 (18.0)7 (7.8) NA31CD117 staining intensity, n (%) < 0.001 Negative1 (14.3)0 (0)0 (0) Weak1 (14.3)9 (18.0)3 (3.3) Intermediate2 (28.6)12 (24.0)5 (5.6) Strong3 (42.9)29 (58.0)82 (91.1)Schlafen 12 staining, n (%)0.083 Negative4 (57.1)12 (24.0)35 (38.9) Positive3 (42.9)38 (76.0)55 (61.1)NA Not available*Association investigated between continuous variables and PDE3A expression using the Kruskal–Wallis test PDE3A expression and tumor characteristics in 147 GISTs NA Not available *Association investigated between continuous variables and PDE3A expression using the Kruskal–Wallis test The second GIST series consists of 26 FFPE tumor samples on TMAs, collected at the National Paediatric and Adult Wild-Type GIST and GIST Clinic at Cambridge University Hospitals NHS Foundation Trust, UK.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Their mutations were analyzed using Sanger sequencing, as described elsewhere .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The tumors harbored mutations in the following genes: KIT (n = 6), PDGFRA (n = 4), NF1 (n = 4), or one of the SDH genes (SDHA, SDHB, SDHC, SDHD, n = 12).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The study on the GIST and liposarcoma series collected from Helsinki Biobank was approved by the Ethics Committee IV of HUH (HUS/1258/2020).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Permission to use tissue samples and clinical data was granted by Helsinki Biobank (HUS/430/2021 §4) and HUH (HUS/244/2021).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Project-specific consent for this retrospective study was waived since the Finnish Biobank Act provides a lawful basis for research use.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The study of GIST samples collected from Cambridge was approved by Cambridge South Research Ethics Committee (REC reference number CA/5175) and all patients provided informed consent.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Mouse monoclonal anti-PDE3A antibodies were produced by immunizing mice with a peptide (amino acids 669–1141) from the catalytic domain of PDE3A (ProteoGenix SAS, Schiltigheim, France) and provided for the study by Sartar Therapeutics Ltd. (Helsinki, Finland).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

After spleen cell fusion and screening of hybridoma supernatants by ELISA, 99 positive clones were identified.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

From these, the supernatants of the 20 clones with the highest binding affinity were selected for testing in immunohistochemistry on FFPE colon tissue, using interstitial cells of Cajal as a positive control for specific staining.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The four clones that showed the highest specificity were subcloned and monoclonal antibodies affinity-purified and further investigated using immunohistochemistry.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Finally, clone 230-F8-G1 was selected to be used in immunohistochemistry.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

TMA Sects. (

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

3 µm thick) were placed on Superfrost® Plus objective slides (Thermo Scientific, MA, USA) and warmed at 56 °C for 30 min following paraffin removal in xylene, followed by a graded alcohol-to-water wash.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Endogenous peroxidase activity was blocked by incubating the slides in 0.8% hydrogen peroxide for 30 min.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Heat-induced epitope retrieval was performed using EnVision FLEX Target Retrieval LOW Solution (Cat# K8005, pH 6.0; Dako, CA, USA) in a HIER Decloaking Chamber (Biocare Medical, CA, USA) at 95 °C for 15 min.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The PDE3A antibody was diluted to 9.2 µg/mL in ImmunoLogic Normal Antibody Diluent (Cat# BD09-500, WellMed, Duiven, Netherlands) and incubated on tissues for 30 min at room temperature in a humidity chamber.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

A secondary antibody (BrightVision 1-step detection system rabbit HRP, Cat# DPVM110HRP, WellMed) was then applied for 30 min under the same conditions.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Antibody binding was detected using the ImmPACT DAB Substrate kit (Cat# SK4105, Vector Laboratories, CA, USA) for 5 min.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

SLFN12 expression was assessed as previously described, using a polyclonal SLN12 rabbit antibody (Cat# PA5-114360, Thermo Scientific) .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Finally, tissues were counterstained with Mayer’s Hematoxylin (Cat# S3309, Dako) for 3 min at room temperature, then dehydrated through a graded alcohol series to xylene.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Sections were washed with Tris-buffered saline containing 0.1% Tween-20 before and after antibody incubation steps.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

CD117 expression was assessed as described elsewhere .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Syncytiotrophoblasts in placental tissue served as a positive control for SLFN12 staining, and staining intensity was categorized as either negative or positive.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Interstitial cells of Cajal in colon tissue served as a positive control for PDE3A staining.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Bone marrow tissue for megakaryocyte PDE3A expression was also assessed.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The stained slides were digitalized using a 20 × objective and with a Panoramic scanner (3DHISTECH, Budapest, Hungary) in Helsinki Biobank and scored manually using SlideViewer software (version 2.7.0.191696, 3DHISTECH).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Due to the homogeneous staining pattern, PDE3A staining intensity was graded into four categories: absent, low, intermediate, and strong (0 to 3).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

GISTs were analyzed independently by three pathologists (O.G., M.S., T.B.).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

For statistical analysis, the average of the scores was calculated and rounded to the nearest whole number.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

RNA was extracted from 30 GIST and 10 liposarcoma FFPE tissue sections using QIASymphony RNA kit and QIASymphony SP instrument (Qiagen GmbH, Hilden, Germany), and 2 µL of RNA (30 to 300 ng) was reverse-transcribed into cDNA using SuperScript™ VILO™ cDNA synthesis kit (Cat# 11754250, Thermo Ficher Scientific, Carlsbad, CA, USA) following the manufacturer’s instructions, as described earlier .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

RNA extracted from the FFPE sample made from the GIST882 cell line was used as a reference sample.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Quantitative PCR was conducted using QuantiNova Probe PCR kit (Cat# 208254, Qiagen), and primers and probe in a ready-to-use mixture for PDE3A expression were designed with QuantiNova LNA PCR software (https://geneglobe.qiagen.com/fi/customize/pcr/mrna-incrna/quantinova-lna-probe-pcr-custom-assays).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

YWHAZ served as a reference gene (Forward: 5´-CGT TAC TTG GCT GAG GTT GC-3’; Reverse: 5’ -TGC TTG TTG TGA CTG ATC GAC-3’; Probe #9: Cat# 04683633001, Universal ProbeLibrary, Roche, Basel, Switzerland).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Real-time PCR was performed using the CFX96 Real-Time System (Bio-Rad Laboratories Inc., Hercules, CA, USA) to triplicate samples under following cycling: initial denaturation at 95 °C for 2 min, followed by 50 cycles at 95 °C for 30 s and at 60 °C for 30 s with plate reading.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Relative PDE3A mRNA expression was calculated using the ΔΔCt method and normalized to YWHAZ expression.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Crosstabs were analyzed using either Fisher’s exact test or Fisher–Freeman–Halton test.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The association between PDE3A expression and continuous variables was analyzed using the Kruskal–Wallis test.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Inter-rater concordance was estimated using Fleiss’ kappa analysis.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Overall survival was calculated from the date of diagnosis to the date of death, and metastasis-free survival from the date of diagnosis to the date of detected metastasis, censoring the patients without events at the end of follow-up.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Survival was estimated using the Kaplan–Meier method and compared using a log-rank test.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Statistical analyses were performed using IBM SPSS Statistics version 29.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Immunohistochemical staining of PDE3A was first investigated in healthy colon tissue.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

We observed strong PDE3A staining in interstitial cells of Cajal, the suggested precursors of GIST, and in mast cells (Fig. 1).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Additionally, endocrine cells within villi, endothelial cells, and ganglia showed weaker expression.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Contrary to a previous study , we did not observe staining in thrombocytes or megakaryocytes in two bone marrow samples, although histiocytes showed granular staining pattern.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Fig. 1Examples of immunohistochemical stainings in healthy and tumor tissues.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

PDE3A expression in (A) Interstitial cells of Cajal, B neuroendocrine epithelial cells and mast cells, and (C) ganglia cells in colon.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Examples of (D) weak, E intermediate, and F) strong staining of PDE3A in GISTs.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

G PDE3A staining was absent in megakaryocytes and showed granular staining in histiocytes in bone marrow tissue samples.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

H Examples of SLFN12-negative and (I) SLFN12-positive and (J) weak, K intermediate, and (L) strong CD117 staining in GISTs.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Each field of view corresponds to 0.2 mm × 0.2 mm Examples of immunohistochemical stainings in healthy and tumor tissues.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

PDE3A expression in (A) Interstitial cells of Cajal, B neuroendocrine epithelial cells and mast cells, and (C) ganglia cells in colon.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Examples of (D) weak, E intermediate, and F) strong staining of PDE3A in GISTs.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

G PDE3A staining was absent in megakaryocytes and showed granular staining in histiocytes in bone marrow tissue samples.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

H Examples of SLFN12-negative and (I) SLFN12-positive and (J) weak, K intermediate, and (L) strong CD117 staining in GISTs.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Each field of view corresponds to 0.2 mm × 0.2 mm An IHC analysis was conducted on the GIST series from Cambridge, where all 26 GISTs were positive for PDE3A staining.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Of these, four (15.4%) had weak, 12 (46.2%) intermediate, and 10 (38.5%) strong staining (Supplementary Table 1).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Similarly, in the Helsinki Biobank series, all GISTs (n = 147) expressed PDE3A with staining intensity varying; seven cases (4.8%) showed weak, 50 (34%) intermediate, and 90 (61.2%) strong staining.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Weak to strong PDE3A expression was observed in all investigated GISTs (Fig. 1; Supplementary Fig. 1).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Inter-rater agreement among the three pathologists for the results from the Helsinki Biobank series was assessed using Fleiss'kappa.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The analysis yielded a kappa (κ) value of 0.692 (standard error = 0.048, 95% confidence interval = 0.60 to 0.79, p < 0.001), indicating substantial agreement between the raters.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Next, we investigated the correlation between PDE3A protein and mRNA expression in GIST and pleomorphic liposarcoma tissues.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Pleomorphic liposarcomas were selected for the comparison as they contain frequently low PDE3A mRNA and protein expression .

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

RT-qPCR was successfully performed on 23 GIST and 10 liposarcoma samples.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Tissue for IHC was available in all GISTs and in 7 liposarcomas.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Relative mRNA expression levels were compared with RNA extracted from a FFPE GIST882 cell line.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

The results demonstrated that PDE3A mRNA expression is significantly higher in GISTs than in liposarcomas (median relative gene expression: 2.30 vs. 0.03, p < 0.001; Fig. 2; Supplementary Table 2).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

In addition, PDE3A protein and mRNA expression levels showed a strong positive correlation (p < 0.001).Fig.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

2Comparison of relative PDE3A mRNA expression and PDE3A protein expression in 23 GIST and 10 liposarcoma tissues.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Immunohistochemistry results were missing for three liposarcomas.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Three GISTs with intermediate staining were grouped in the strong staining category.

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

A PDE3A mRNA expression was significantly higher in GISTs than in liposarcomas (p < 0.001).

PMC12647229

Phosphodiesterase 3 A expression in gastrointestinal stromal tumors

Examples of (B) PDE3A-negative and (C) PDE3A weak staining in liposarcomas.